Dengue fever in a tertiary hospital
in Makkah, Saudi Arabia
W. Shahina,b#, A. Nassara,c, M. Kalkattawia and H. Bokharia
a
b
Internal Medicine Department, Al Noor Specialist Hospital,
King Abdullah Medical City, Makkah, Saudi Arabia
Tropical Medicine Department, Benha University, Benha, Egypt
Dermatology Department, Tanta University, Tanta, Egypt
c
Abstract
Dengue fever is endemic in the western part of Saudi Arabia. This study aimed at describing the clinical
and laboratory profiles of dengue fever patients admitted to a tertiary hospital in Makkah, Saudi Arabia,
from 2006 to 2008.
A total of 159 dengue fever patients were admitted during the spring and early summer. Their mean
age was 25.6±16.1 years. Males outnumbered females by a ratio of 2:1. Of them, 143 patients (89.9%)
had classic dengue fever and 16 patients (10.1%) had dengue haemorrhagic fever (DHF); one of them
developed severe dengue shock syndrome (DSS) and died (0.6%). The common symptoms were highgrade fever, headache and body aches (100%), nausea and vomiting (27%), retro-orbital pain (25%),
skin rash (16.4%), dry cough (8.2%) and haemorrhagic manifestations (3.14%). The main laboratory
abnormalities were leukopenia (WBCs less than 4000/cmm) in 53.7% of patients, thrombocytopenia
(platelet count less than 100 000/cmm) in 36.2% of patients and prolonged partial thromboplastin time
(PTT) (>1.5 times of control value) in 33% of patients. Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) were elevated more than five-fold in 35.2% of patients. The mean AST/ALT were
226.7/164 U in DF while in DHF these were 555/314 U. Twenty-six patients (16.4%) developed skin
rash and had a significantly lower ALT value and a higher platelet count than those without rash.
Keywords: Dengue virus; dengue haemorrhagic fever; Makkah; Saudi Arabia; clinical symptoms; AST/ALT ratio.
Introduction
Dengue fever (DF) is one of the world’s major
re-emerging infections. In recent decades, there
has been an expanded geographical distribution
of the virus and the mosquito vector, increased
#
epidemic activity, and the emergence of dengue
haemorrhagic fever (DHF) in new geographical
regions.[1] The disease is endemic in more than
100 countries and around 2500 million people
are at risk. WHO estimates that there may be
50 million cases of dengue infection worldwide
E-mail: [email protected]; Tel.: 00966507971162; Fax: 0096625668276
34
Dengue Bulletin – Volume 33, 2009
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
every year.[2,3] The reasons for the emergence of
dengue haemorrhagic fever are complex and
not fully understood but demographic, social
and public health infrastructure changes in the
past decades have contributed greatly to this
phenomenon[4].
Dengue virus belongs to the genus
Flavivirus, family Flaviviridae. It is composed
of single-stranded RNA and has four
antigenically-related but distinct serotypes
(DENV-1, DENV-2, DENV-3 and DENV-4).
It is transmitted by the bite of Aedes aegypti
mosquito. [5] According to WHO, dengue
virus can cause classic dengue fever, dengue
haemorrhagic fever and dengue shock
syndrome (DSS). [6] Outbreaks have been
more common in West Asia in the 1990s,
with a major epidemic occurring in Jeddah,
Saudi Arabia, in 1994.[7] A few reports on the
epidemic were published after 2001.[8,9,10]
Many factors contribute to the recognition
of such outbreaks, which include increased
awareness on the part of medical authorities
and more exposure of populations to the
mosquito vector, especially in low-standard
areas and in the peripheral region of towns
where solid waste disposal is suboptimal.
This study aimed at reporting the
demographic, clinical and laboratory data along
with the disease outcome of all dengue patients
admitted to Al Noor Hospital, Makkah, during
the period 2006–2008, and comparing the
characteristics between those with simple and
complicated disease, which may aid in improved
recognition of the disease in the area.
Materials and methods
Study site and population
This study was conducted on 159 patients
admitted with diagnosis of dengue infection
Dengue Bulletin – Volume 33, 2009
to Al Noor Specialist Hospital, Makkah, from
2006 to 2008. Makkah is a holy city for
Muslims from all over the world. It is located
in the western province of Saudi Arabia, about
70 km from the Red Sea (Jeddah city). It is the
third largest city in Saudi Arabia after Riyadh
and Jeddah. It has a population of about 3
million and receives about four million visitors
a year. Al Noor Specialist Hospital is a 600-bed,
well-equipped, tertiary-level hospital. It is the
main hospital in Makkah. It actually serves the
entire local community as well as visitors as it
is only 3 km away from the holy mosque. All
age groups, including paediatric patients, are
admitted there.
Study design
All patients presented to the emergency room
with high fever, bone pains and bicytopenia
were admitted as cases of “fever and bicytopenia
for investigation” and were fully investigated.
The diagnosis was revised on discharge and
the final diagnosis was implemented on the
Hospital Information System (HIS) according
to the disease coding system ICD-10 AM
(International Classification of Disease-10,
Australian Modification), version 2006. Data
were collected retrospectively by reviewing the
HIS and the patient discharge summary.
The data studied included age, sex,
nationality and the presence of fever,
constitutional symptoms, skin rashes and
bleeding tendency. Investigations included
complete blood count, liver function tests and
coagulation profile (PT, PTT and INR). Tests for
fever of unknown origin were conducted and
these included: bacterial cultures, serology for
Salmonella and Brucella and serology for viruses
(hepatitis viruses A, B and C, cytomegalovirus
and infectious mononucleosis virus). Thin and
thick blood films were examined for malaria
parasites.
35
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
Sera from all suspected cases were
tested in the Central Laboratory of the
Ministry of Health in Jeddah for anti-dengue
immunoglobulins (IgM) by enzyme-linked
immunoassay (ELISA) and for the dengue virus
RNA by polymerase chain reaction (RT-PCR).
The results were either positive or negative for
dengue fever. It must, however, be mentioned
that serotyping was not done in this study.
The diagnosis of dengue fever depended on
the clinical and laboratory findings and positive
serology according to WHO criteria.[6]
Statistical analysis
All data were entered and analysed using
Microsoft Office Excel 2007.
Results
All patients tested positive for anti-dengue
immunoglobulins (IgM-ELISA) and/or dengue
virus RNA by polymerase chain reaction
(RT-PCR). They had negative cultures and
negative serology for Salmonella, Brucella,
viral hepatitis, cytomegalovirus and infectious
mononucleosis virus infections. Also, thin and
thick blood films for malaria were negative.
Seasonality
Thirty nine patients were admitted during
2006, 97 during 2007 and 23 during 2008.
Most of the patients were admitted during the
spring and early summer (April, May and June)
(123/159, 77.4%) (see Figure).
Figure: Monthly distribution of dengue fever patients admitted during 2006–2008
36
Dengue Bulletin – Volume 33, 2009
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
Two thirds of the patients were Saudi
(67%), only two patients were visitors (pilgrims
for Hajj), while all others were residents of
Makkah. The mean age was 25.6±16.1 years
(range 4 to 81 years). All age groups, including
children, were admitted; the percentage of
children below the age of 12 years was only
24%. The age distribution is shown in Table
1. The male to female ratio was 2:1 (107
M:52 F).
Table 1: Age distribution of
dengue fever patients
Age
(Years)
Number of patients (%)
(Total =159)
Up to 12
38 (24.0%)
13–20
47 (30.0%)
21–30
32 (20.0%)
31–40
17 (10.5%)
41–50
17 (10.5%)
>50
8 (5.0%)
According to WHO criteria,[6] 143 patients
(89.9%) were diagnosed as classic DF and 16
patients as DHF (10.1%), five of them had
clinically significant bleeding (3.1%) and one
patient died because of severe DSS (0.6%).
Plasma leakage, which is the hallmark of
DHF, could not be fully assessed since it is
a retrospective study and no routine serial
follow-up of complete blood count (CBC),
chest X-ray (CXR) or ultrasound to document
plasma leakage was undertaken unless it was
clinically significant.
Clinical manifestations
All patients had headache, bodyaches and
high-grade fever. Fever was more than
Dengue Bulletin – Volume 33, 2009
38.5 °C for an average of 4.83±2.48 days
before admission (range: 1 to 14 days). Two
male patients presented with fever and coma
on top of chronic liver disease and were
diagnosed as hepatic encephalopathy and
dengue fever; they improved on supportive
treatment. One patient presented with shock
and gastrointestinal bleeding; the endoscopy
showed haemorrhagic gastritis and the mucosa
was oozing blood. This patient died after two
days in the intensive care unit because of
irreversible shock (Table 2).
It is not possible to revise the clinical data
according to the new WHO guidelines (2009)[11]
for severe and non-severe dengue as these were
published after the end of the study.
Laboratory investigations
The haematological abnormalities were
thrombocytopenia and leukopenia. Platelet
count less than 100 000/cmm was seen in
36.2% of patients and less than 50 000/
cmm in 6.9% of patients. The white blood
cell count was less than 4000/cmm in 53.7%
of patients and less than 2000/cmm in 9.3%
of patients. Partial thromboplastin time was
1.5-fold higher than the upper normal level
in 33.3% of patients, while prothrombin time
and INR were normal in all patients. The AST
and ALT values were five-fold more than the
upper normal levels in 56 patients (35.2%).
The AST value was ten-fold more than the
upper normal level in 23 patients (14.5%),
while ALT value was ten-fold more than the
upper normal level in 14 patients (8.8%), and
AST/ALT ratio was 1.38:1.
Five patients presented with DHF and with
clinically significant levels of bleeding; they
were four males and one female and all were
non-Saudi, the average age being 20.8±9.8 (8
to 37). Haemoglobin was lower than 12 gm/dl
37
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
Table 2: Clinical manifestations of patients with dengue fever
Clinical manifestations
n (%)
Fever
159 (100%)
Headache/bodyache
159 (100%)
Retro-orbital pain
40 (25%)
Chills and rigours
34 (21.4%)
Gastrointestinal symptoms
Upper
Nausea and vomiting
43 (27.0%)
Lower
Abdominal pain and diarrhoea
39 (24.5%)
Skin rash: Total
26 (16.4%)
Morbilliform
15/26 (57.7%)
White islands in a sea of red
8/26 (30.8%)
Sunburn-like erythema of the face
3/26 (11.5%)
Respiratory symptoms (dry cough and sore throat)
13 (8.2%)
Haemorrhagic manifestations (five patients)
5(3.14%)
Haematemesis and melena
2 (40%)
Epistaxis and hemoptysis
1 (20%)
Haematuria
1 (20%)
Puerperal haemorrhage
1 (20%)
Others (hepatic encephalopathy)
2 (1.3%)
Mortality (one patient)
1 (0.6%)
n=number of patients (159)
%=percentage of patients with studied clinical manifestation to the total number of patients and the group.
and WBC count was above 4000/cmm in
all patients. The platelet count was below
100 000/cmm in three patients (60%) and
PTT was above normal in all patients. In all
patients, ALT was above five-fold, and AST was
above ten-fold. Table 3 shows that the patients
presented with bleeding had less platelet count
and more prolonged PTT, and significantly
higher WBCs, AST and ALT values.
38
Twenty-six patients had skin rashes and
dengue fever; the skin rash ranged from
morbilliform (15 patients), white islands in
a sea of red (eight patients) to sunburn-like
erythema of the face (three patients) (Table 2).
It was found that the patients who presented
with rash had a statistically insignificant lower
WBCs count and AST values while the platelet
count was significantly higher and ALT value
was significantly lower (Table 4).
Dengue Bulletin – Volume 33, 2009
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
Table 3: Comparison of laboratory findings between DF and DHF patients
presented with bleeding
DF patients
Mean±SD (range)
DHF patients with
bleeding
(5 patients)
Mean±SD (range)
Platelets
(150–400x103/cumm)
124±72.8x103
(6–340)
101±54
(45–161)
>0.05
WBCs
(4–11x 103/cumm)
3.94±2.05x103
(0.9–9.9)
8±2.6
(5.2–11.3)
<0.05
PTT (28.6–38.2 sec)
45.69±9.6
(32–71 )
47.6±8.2
(39.3–55.6)
>0.05
AST (15–37 IU/L)
226.7±190
(45–980)
555±183
(425–685)
<0.05
ALT (17–41 IU/L)
164±119.5
(31–458)
314±26
(295–333)
<0.05
Parameter
P value
SD=standard deviation
ALT=alanine aminotransferase
AST=aspartate aminotransferase
PTT=partial thromboplastin time
WBCs=white blood cells
Table 4: Comparison between laboratory results in dengue fever patients
with and without skin rash
Without skin rash (133)
Mean±SD (range)
With skin rash (26)
Mean±SD (range)
Parameter
P value
4.15±2.13
(0.9–9.9)
3.9±2.29
(1.9 to 9.9)
WBCs
(4–11x103/cumm)
>0.05 (0.717)
112.34±65.5
(6–340)
171±86.3
(6–330)
Platelets
(150–400x103/cumm)
<0.05 (0.010)
257.96±207
(47–980)
119±25.49
(45–165)
AST
(15–37 IU/L)
>0.05 (0.072)
180±126.5
(31–458)
84.2±45.1
(22–182)
ALT
(17–41 IU/L)
<0.05 (0.026)
SD=standard deviation
ALT=alanine aminotransferase
AST=aspartate aminotransferase
PTT=partial thromboplastin time
WBCs=white blood cells
Dengue Bulletin – Volume 33, 2009
39
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
Course of the illness
All patients were treated symptomatically with
intravenous fluids and analgesics. Fresh frozen
plasma, platelet and blood transfusion were
given only when needed, according to WHO
criteria. The length of stay in the hospital
varied from one to nine days with an average
of 4.07±1.48 days. All patients improved,
except one male, non-Saudi patient, who
developed severe DSS and died. Patients
were discharged from hospital, according to
WHO criteria for discharging patients which
include: absence of fever for at least 24 hours
without the use of anti-fever therapy, return
of appetite, visible clinical improvement, good
urine output, minimum of three days after
recovery from shock, no respiratory distress
from pleural effusion, and no ascites and
platelet count of more than 50 000/cmm.[6]
In the present study, most of the cases
were admitted in the spring and early summer
(77%); cases were also reported from Jeddah.[10]
While in tropical areas most of the epidemics
happen in the post-rainy season in the autumn
months,[12] it is important to mention that
it seldom rains in Makkah and Jeddah but
there are swamps and inadequate sanitary
facilities in some areas. While dengue fever
is an important health problem for travellers
to all endemic areas, including Makkah, only
two of the patients were visitors (for Hajj) and
the others were non-Saudi patients resident in
Makkah. The reason for a lesser number of Hajj
patients could be because of good sanitation
and mosquito control in Hajj residency areas.
(The risk of exposure to dengue fever can be
minimized in modern, air-conditioned hotels
with well-kept grounds.[13])
This study signifies the special pattern of
dengue fever in the western part of Saudi
Arabia, which is different from other parts of
Asia; it happens more in adults and males,
has different seasonality, has less morbidity
and mortality, and does not constitute a major
health problem for visitors to holy places.
The mean age of patients was 25.6±16.1
years and the percentage of infected children
was 24%; in Jeddah the mean age was
27.6±11.2 years and the percentage of
children was 6%.[10] Internationally, dengue
fever is an infectious disease of children.
Reports from India, Sri Lanka, Indonesia and
Thailand indicate that children may constitute
up to 95% of cases and the peak age of
contracting dengue infection is between 5
and 10 years.[14-18]
Epidemics of dengue fever have been
reported from the Arabian Peninsula since the
late 19th century, affecting many major cities
such as Aden, Jeddah, Makkah and Madinah.
[7]
Dengue fever virus was first isolated in
Jeddah in 1994 from a fatal case of DHF; since
that time, all medical personnel in the area
were alerted and a surveillance system was
established by the Ministry of Health. From
1994 to 1999, a total of 207 cases of dengue
fever were reported;[8] since then, sporadic
cases have continued to be reported from
Jeddah and Makkah.
It is clear that the age pattern of dengue
fever infection in Saudi Arabia is different
from that of South-East Asia, and is closer to
the age pattern of dengue fever infection in
Brazil, where it is the highest in adults. This
may be related to the genotypes present. The
reports from Brazil indicate that DENV-1 and
DENV-2 viruses happen more in adults,[19,20]
and in Jeddah, DENV-1 and DENV-2 viruses
constitute 93% of the cases [9]. Males are
affected more than females (ratio of 2 to 1);
the same is the case in Jeddah[10] while reports
from other endemic areas show that males and
Discussion
40
Dengue Bulletin – Volume 33, 2009
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
females are affected equally.[16,17,21] The less
number of females affected in Saudi Arabia
may be due to their limited outdoor exposure
(for social reasons) and to their wearing the
veil (hijab) outdoors when the whole body
is covered.
As regards the patients’ symptoms, highgrade fever, headache and bone pains were
the most common symptoms, followed by
gastrointestinal complications, chills and
rigours, skin rash and respiratory problems.
Similar findings have been reported by
national[10] and international researchers.[22]
Haemorrhagic manifestations happened in
five patients (3.14%), similar to other reports
in Saudi Arabia and internationally.[10,23] In a
study from Indonesia, out of 1300 cases severe
bleeding was recorded in 76 of the dengue
cases (6%) and included haematemesis (58%),
melena (21%), haematemesis-melena (16%)
and DIC (5%). [20] Two patients presented
with hepatic encephalopathy (1.3%), and
both had chronic liver disease. A report from
Thailand shows that hepatic encephalopathy
was considered an unusual manifestation of
dengue fever and they attributed this to toxic
substance, drugs or underlying liver conditions.
[24]
In rare cases dengue fever may present as
an acute liver failure.[25] One patient presented
with DSS and GI bleeding and died (0.6%).
In the Indonesian study, out of 1300 patients,
102 patients (8%) had DSS and 17 patients
died (1.3%).[20] About 36.2% of patients had
a platelet count of less than 100 000/cmm,
which is less than the international figure
(58%)[26]. The lower percentage of DSS and
thrombocytopenia in this study compared
to the international figures perhaps because
of the limited number of cases; also, it is
necessary to do more frequent investigations
to detect early and mild cases of plasma
leakage (such as CBC, abdominal ultrasound
and CXR).
Dengue Bulletin – Volume 33, 2009
Patients who developed bleeding were
not necessarily those who had the lowest
platelet number, which means that bleeding
is a multifactorial process; bleeding may
result from a combination of factors such as
thrombocytopenia, coagulation defects and
vasculopathy.[20] The average number of white
cell count was 3940±2050 and 53.7% of the
patients had WBCs less than 4000/cmm; this
was close to a local study[10] where 48.72% of
patients had WBC below 4000/cmm. Also,
in a study from South-East Asia, the mean
WBCs was 3834±2216 and the percentage of
leukopenia below 5000/cmm was 89.77%[26].
Prolonged PTT more than 1.5-fold the upper
normal limit was found in one third of the
patients; this was similar to reports from
Jeddah, Thailand and India.[10,15,22]
The liver is a target organ of dengue
infection; hepatic involvement ranged from
mildly elevated aminotransferases to fulminant
hepatic failure leading to death.[27-30] The
pathology included severe, diffuse hepatitis,
focal necrosis of hepatic cells and hyaline
necrosis of Kupffer cells.[31,32,33] Liver function
tests showed elevated liver enzymes with
normal bilirubin and alkaline phosphatase,
liver enzymes were higher than five-fold the
upper normal limit in 56 patients (35.2%);
it was also elevated as reported from Saudi
Arabia and Thailand in 66.7%, 63%, 67% and
34.2% of patients.[10,27,34,35] It is worth noting
that the level of AST elevation was higher than
that of ALT (ALT/AST ratio of 1:1.38) in contrast
to acute viral hepatitis; this finding was also
reported from South-East Asia[24].
Sixteen patients had DHF (10.1%), five
of them presented with overt bleeding; the
average age was 20.8±9.8 (8 to 37), similar
to reports from Brazil[20] but different from
South-East Asian patients where most of them
were children.[18] Liver enzymes were higher
than those with classic dengue fever and the
41
Dengue fever in a tertiary hospital in Makkah, Saudi Arabia
AST/ALT ratio was higher at 1.77:1 while it was
1.38:1 in dengue fever patients. In South-East
Asia, 92% of patients with DHF had AST more
than 60U, and in patients who presented with
encephalopathy, AST and ALT values usually
exceeded 200U.[24] The frequency of hepatic
dysfunction depends on dengue fever disease
severity. There was a correlation between liver
enzymes and the severity of dengue infection.
[36]
The appearance of rash may be associated
with the milder illness of classic DF.
The prevalence of dengue fever in Saudi
Arabia is not unique. WHO has described
the presence of dengue in other areas of the
Eastern Mediterranean Region – in Egypt
as early as in 1979, in Sudan (1985) and in
Djibouti (1991). In Saudi Arabia, three major
epidemics have been reported: a DENV-2
epidemic in 1994 with 469 cases of dengue,
23 cases of DHF, two cases of DSS and two
deaths; a DENV-1 epidemic in 2006 with 1269
cases of dengue, 27 cases of DHF, 12 cases of
DSS and six deaths; and a DENV-3 epidemic in
2008 with 775 cases of dengue, nine cases of
DHF, four cases of DSS and four deaths[36].
The limitations of this study are due
mainly to its retrospective type, limited
number of cases, inability to know the total
number of suspected cases, and lack of
frequent investigations to pick up early cases of
plasma leakage. These issues should be taken
into consideration in later studies.
In conclusion, dengue fever is an endemic
disease in Makkah, the holy city for Muslims. It
is rare in visitors who come to Makkah for the
Hajj pilgrimage, but all measures to prevent
the spread of the disease should be taken.
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